Danger signals: Chemotherapy enhancers?

Endogenous danger signals are molecules normally present in a given cell compartment that are rapidly released following cell stress and induce immune responses. We and others have shown that dying tumor cells treated with some chemotherapies are able to induce anticancer immune responses, which rely on their release of danger signals such as the nuclear protein HMGB1. DNA can also be released from chemotherapy-treated tumor cells, act as a danger signal, and boost anticancer immunity. While the immunostimulatory properties of DNA have been identified for decades, the recent discovery of a novel family of receptors, cytosolic DNA sensors, has provided a novel impetus not only to understand how chemotherapy can trigger anticancer immune responses but also to exploit DNA-derived molecules for therapeutic use. We will here discuss the molecular characteristics of endogenous danger signals released from chemotherapy-treated tumor cells and focus on the clinical relevance of using these danger signals in chemoimmunotherapeutic strategies against cancer.